A need existed, heretofore, for a method of administering drug to a preselected tissue compartment of the eye. More particularly, the need existed for a method that both administers drug to a preselected tissue compartment and controls the delivery of drug to achieve a well-defined concentration in the tissue compartment. This particular need existed because of the shortcomings associated with some of the prior art methods for administering drugs, mainly drops and ointments. For example, these methods are unsatisfactory because drops and ointments both result in the eye receiving drug that is administered indiscriminately to all tissue compartments including tissue compartments that do not need medication, and because these methods do not permit that the drug administered be kept at a well-defined concentration in the tissue compartments of the eye. Also, drops and ointments are wasteful, as they use excessive amounts of drug for treating a condition that can be treated with less drug, and because the drug is washed away by tears leaving the eye without drug until the next application of drug. Often, the tissue compartments receiving medication they do not need may exhibit unwanted side effects to the drug. See U.S. Pat. Nos. 3,149,035; 3,214,338; 3,415,929; 3,856,919; 3,872,865; 4,003,991; and Journal of Pharmaceutical Sciences, Volume 63, Number 3, pages 335 to 338, 1974.
Another prior art method for administering drug to the eye consisted in applying a lamella to the inner surface of the eyelid. Usually, lamella were made by dispersing drug in a water-soluble gel of glycerinated gelatin that dissolved rapidly in tear fluid producing the same effects obtained with drops and ointments. These effects include administering drug to all tissues of the eye, even to tissues that do not need medication. That is, lamella lack the ability to administer drug to preselected tissues compartments, and they do not possess any properties for evidencing any relation between the amount of drug administered and the concentration of drug in the tissue compartments of the eye. See Great Britain 1451, and in United States Patent No. 273,410; Pharmaceutical Sciences, by Remington, Volume XII, pages 547 to 548, 1965, published by Mack Publishing Company, Easton, PA, and An Introduction to Pharmaceutical Formulation, by Fishburn, Chapter 6, page 116, 1965, published by Pergamon Press Ltd. New York.
Ocular therapeutic systems for administering drug to the eye are known to ocular pharmacology and ophthalmic therapy in U.S. Pat. Nos. 3,416,530; 3,618,304; and 3,828,777, in United States Patent Application Ser. No. 569,953 filed on Apr. 21, 1975 and in United States Patent Application Ser. No. 578,979 filed on May 19, 1975. These patents and the patent applications are assigned to the ALZA Corporation of Palo Alto, Calif., the assignee of this patent application. The ocular systems disclosed in the patents and applications provide a complete ophthalmic course of therapy by administering drug for a prolonged period of time to the eye to produce a beneficial effect. These systems are made with a drug reservoir, a rate controller and a portal for releasing drug in a controlled therapeutic pattern to the eye and its surrounding tissues.
While the above ocular therapeutic systems are truly outstanding and represent a pioneering advancement in ocular drug delivery, and while they are useful for administering drug to the total environment of the eye, there are instances where the use of these systems can be inventively improved for more desirable therapy. For example, this invention makes possible the obtainment of the therapeutic benefit of a chosen drug and to control its concentration in a preselected tissue compartment by a preplanned cooperation, between the therapeutic system and the tissue compartment, effected through specific, directional controlled drug delivery in correlation with its concentration in a tissue compartment of the eye. The prior art lack of directional control coupled with a correlation in drug delivery makes it difficult to obtain the full therapeutic effect of a chosen drug and to regulate its concentration in the tissue compartment; particularly, if the drug is released to a tissue compartment distant and remote from the tissue compartment that really needs specific medication. The prior art methods of non-specific drug administration are wasteful, as they administer excessive drug that is lost through the nasolacrimal duct, by a rapid runoff of a swollen tear film, and because they administer drug to tissue compartments that do not need it. With these non-specific methods of administration, only a fraction of drug remains available for penetration into a preselected tissue compartment, or for introduction at a specific loci of the eye for entrance into systemic circulation.